Methods for Population Adjustment with Limited Access to Individual Patient Data: A Review and Simulation Study

Population-adjusted indirect comparisons estimate treatment effects when access to individual patient data is limited and there are cross-trial differences in effect modifiers. Popular methods include matching-adjusted indirect comparison (MAIC) and simulated treatment comparison (STC). There is limited formal evaluation of these methods and whether they can be used to accurately compare treatments. Thus, we undertake a comprehensive simulation study to compare standard unadjusted indirect comparisons, MAIC and STC across 162 scenarios. This simulation study assumes that the trials are investigating survival outcomes and measure continuous covariates, with the log hazard ratio as the measure of effect. MAIC yields unbiased treatment effect estimates under no failures of assumptions. The typical usage of STC produces bias because it targets a conditional treatment effect where the target estimand should be a marginal treatment effect. The incompatibility of estimates in the indirect comparison leads to bias as the measure of effect is non-collapsible. Standard indirect comparisons are systematically biased, particularly under stronger covariate imbalance and interaction effects. Standard errors and coverage rates are often valid in MAIC but the robust sandwich variance estimator underestimates variability where effective sample sizes are small. Interval estimates for the standard indirect comparison are too narrow and STC suffers from bias-induced undercoverage. MAIC provides the most accurate estimates and, with lower degrees of covariate overlap, its bias reduction outweighs the loss in effective sample size and precision under no failures of assumptions. An important future objective is the development of an alternative formulation to STC that targets a marginal treatment effect.Comment: 73 pages (34 are supplementary appendices and references), 8 figures, 2 tables. Full article (following Round 4 of minor revisions). arXiv admin note: text overlap with arXiv:2008.0595

The Mine Action Information Center and The State Department’s Humanitarian Demining Fellowship: Molding the Future of the Landmine Community

James Madison University (JMU) is host to the State Department’s Mine Action Information Center (MAIC). The MAIC has given many students the opportunity, whether through local employment or the State Department’s Humanitarian Demining Fellowship, to learn and experience mine action. Today, many of JMU’s former students are players in the global landmine community

Exergame design for elderly users: the case study of SilverBalance

In this paper, we discuss chances and challenges of game design for an elderly audience with a focus on the development of safe and usable exertion games for frail senior citizens. Based on an analysis of theoretical constraints, we conducted a case study which implements different balance tasks for elderly players featuring the Nintendo Wii Balance Board which encourages users to actively engage in game play. Furthermore, we tested the feasibility of the board as input device for our case study SilverBalance. Our results indicate that age-related impairments influence the use of video games among frail elderly in many respects, hence their needs have to be considered during the design process. In this context, our paper provides a foundation for future research regarding digital games for the elderly. © 2010 ACM

A Multitask Diffusion Strategy with Optimized Inter-Cluster Cooperation

We consider a multitask estimation problem where nodes in a network are divided into several connected clusters, with each cluster performing a least-mean-squares estimation of a different random parameter vector. Inspired by the adapt-then-combine diffusion strategy, we propose a multitask diffusion strategy whose mean stability can be ensured whenever individual nodes are stable in the mean, regardless of the inter-cluster cooperation weights. In addition, the proposed strategy is able to achieve an asymptotically unbiased estimation, when the parameters have same mean. We also develop an inter-cluster cooperation weights selection scheme that allows each node in the network to locally optimize its inter-cluster cooperation weights. Numerical results demonstrate that our approach leads to a lower average steady-state network mean-square deviation, compared with using weights selected by various other commonly adopted methods in the literature.Comment: 30 pages, 8 figures, submitted to IEEE Journal of Selected Topics in Signal Processin

Secukinumab versus adalimumab for psoriatic arthritis: comparative effectiveness up to 48 weeks using a matching-adjusted indirect comparison

Secukinumab and adalimumab are approved for adults with active psoriatic arthritis (PsA). In the absence of direct randomized controlled trial (RCT) data, matching-adjusted indirect comparison can estimate the comparative effectiveness in anti-tumor necrosis factor (TNF)-naïve populations. Individual patient data from the FUTURE 2 RCT (secukinumab vs. placebo; N = 299) were adjusted to match baseline characteristics of the ADEPT RCT (adalimumab vs. placebo; N = 313). Logistic regression determined adjustment weights for age, body weight, sex, race, methotrexate use, psoriasis affecting ≥ 3% of body surface area, Psoriasis Area and Severity Index score, Health Assessment Questionnaire Disability Index score, presence of dactylitis and enthesitis, and previous anti-TNF therapy. Recalculated secukinumab outcomes were compared with adalimumab outcomes at weeks 12 (placebo-adjusted), 16, 24, and 48 (nonplacebo-adjusted). After matching, the effective sample size for FUTURE 2 was 101. Week 12 American College of Rheumatology (ACR) response rates were not significantly different between secukinumab and adalimumab. Week 16 ACR 20 and 50 response rates were higher for secukinumab 150 mg than for adalimumab (P = 0.017, P = 0.033), as was ACR 50 for secukinumab 300 mg (P = 0.030). Week 24 ACR 20 and 50 were higher for secukinumab 150 mg than for adalimumab (P = 0.001, P = 0.019), as was ACR 20 for secukinumab 300 mg (P = 0.048). Week 48 ACR 20 was higher for secukinumab 150 and 300 mg than for adalimumab (P = 0.002, P = 0.027), as was ACR 50 for secukinumab 300 mg (P = 0.032). In our analysis, patients with PsA receiving secukinumab were more likely to achieve higher ACR responses through 1 year (weeks 16-48) than those treated with adalimumab. Although informative, these observations rely on a subgroup of patients from FUTURE 2 and thus should be considered interim until the ongoing head-to-head RCT EXCEED can validate these findings. Novartis Pharma AG

Lag selection of the augmented Kapetanios-Shin-Snell nonlinear unit root test

We provide simulation evidence that shed light on several size and power issues in relation to lag selection of the augmented (nonlinear) KSS test. Two lag selection approaches are considered-the Modified AIC (MAIC) approach and a sequential General to Specific (GS) testing approach Either one of these approaches can be used to select the optimal lag based on either the augmented linear Dickey Fuller test or the augmented nonlinear KSS test, resulting in four possible selection methods, namely, MAIC, GS, NMAIC and NGS. The evidence suggests that the asymptotic critical values of the KSS test tends to result in oversizing if the (N) GS method is used and under-sizing if the (N) MAIC method is utilised. Thus, we recommend that the critical values should be generated from finite samples. We also find evidence that the (N) MAIC method has less size distortion than the (N) GS method, suggesting that the MAIC-based KSS test is preferred. Interestingly, the MAIC-based KSS test with lag selection based on the linear ADF regression is generally more powerful than the test with lag selection based on the nonlinear version

Evaluating social games for kids and teenagers diagnosed with cancer

Serious games for health are interactive games with a focus on health care, physical and mental fitness. As it is assumed that social support can also indirectly influence patient's health condition, multiplayer online health games present an innovative approach of improving the player's health condition. In this paper we present the health game prototype "Adventures in Sophoria" developed at the University of Duisburg-Essen with the goal of facilitating the intercommunication of teenagers during cancer treatment. Two versions of the game were implemented, one explicitly referring to cancer and an implicit version with no cancer content. In a between-subjects experimental study with a clinical sample, both versions were compared. Additionally, parents and nursing staff were interviewed in order to evaluate the demand regarding health games. Results suggest that the implicit game version yielded higher enjoyment and acceptance compared to the explicit version. © 2011 IEEE

Real Exchange Rates over a Century: The Case of the Drachma/Sterling Rate, 1833-1939

Recent studies on real exchange rates advocate the use of long samples in order to reveal the low frequency properties of the processes. The present paper contributes to this strand of the literature by exploiting recently released time series for the drachma/sterling rate for the period 1833-1939. This is an interesting period as it covers different exchange rate regimes and the effects of important historical events. In the paper, the mean-reverting behaviour of the real drachma/sterling exchange rate is initially examined applying univariate unit root tests and then the validity of Purchasing Power Parity (PPP) is tested using cointegration analysis. The results provide support for a weak PPP relationship, which turns out to be robust across different sub-periods characterised by different exchange rate regimes. Adjustment to PPP is reached at a relatively high speed and occurs via movements of the nominal exchange rate.real exchange rates; cointegration; PPP